The ever-increasing prevalence of bacteria harboring extrachromosomal elements or plasmids that confer resistance to chemotherapeutic drugs, that specify production of surface antigens, hemolysins, bacteriocins, toxins and other invasins and/or that alter biochemical traits so as to make clinical identification difficult, is causing curtailment of bacterial infectious diseases to be increasingly more difficult and therefore constitutes a threat to the public health. The objective of our research is to study transmission and functions of plasmids in gram-negative bacteria so as to be able to develop means for effective control and treatment of bacterial diseases. Most of the research will be concerned with R plasmids in Escherichia coli and Salmonella typhimurium and will utilize minicell-producing strains of both of these bacterial species. During the coming year, we will specifically investigate: a) the methodology for the selected translocation of drug resistance elements unto a diversity of plasmid types andthe use of these derived plasmids to facilitate plasmid incompatibility testing; b) the effects of transmission and host genotype on the mechanism of translocation of drug resistance elements; c) the host range and incompatibility of R plasmids from Acintobacter; and d) mechanisms of resistance and sensitivity to serum bacteriacidal killing and the influence of plasmids on such resistance or sensitivity. We will utilize the technologies of microbial genetics, molecular biology, immunology and electron microscopy in this research.